A systematic review of miRNA expression in schizophrenia spectrum disorders across the blood and the brain

Several studies have investigated whether individuals with schizophrenia spectrum disorders (SSD) show altered microRNA expression. However, findings in this field have not been synthesized so far. Therefore, we performed a systematic review of studies measuring microRNA levels in the peripheral blood and brain samples of individuals with SSD and healthy controls. We searched electronic databases for studies comparing the expression of microRNAs between individuals with SSD and healthy controls. We synthesized findings with respect to concordance of alterations across the brain and peripheral blood, observations in early psychosis, medication effects, treatment resistance, molecular pathways and the utility of microRNAs as potential biomarkers. Altogether, 77 studies measuring the expression of 124 dysregulated microRNAs were included. Among them, 35 microRNAs were upregulated and 11 were downregulated in brain samples while 69 microRNAs were up-regulated and 37 were downregulated in blood samples of individuals with SSD. The most consistent finding was the overexpression of miR-181b-5p and miR-34a-5p in 8 out of 10 studies with concordant results across both types of biological materials. Both microRNAs are involved in apoptosis, neurodevelopment, and cell survival. The area under the curve (AUC) values were 0.84 0.08 with the highest AUC observed for miR-199-3p (0.979). The overexpression of miR-181b-5p and miR-34a-5p is the most consistent dysregulation of microRNA expression in SSD, suggesting the significance of apoptotic, neurodevelopmental, and cell survival processes. The analysis of microRNA expression might be promising for the development of potential biomarkers for SSD.